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Biomedical subjects

Axel Scherer

Publications and source records attributed to Axel Scherer.

At least 19 recordsLinked to original sources

Applications of microfluidics for neuronal studies.

Microfabrication processes have changed the technology used in consumer goods, and have now advanced into applications in biology. Microfluidic platforms are microfabricated tools that are gaining popularity for studies of molecular and cellular biology. These platforms can allow precise control of the environment surrounding individual cells and they have been used to study physiologic and pharmacologic responses at the single-cell level. This article reviews microfluidic technology with emphasis on advances that could apply to the study of the nervous system, including architecture for isolation of axons, integrated electrophysiology, patterned physical and chemical substrate cues, and devices for the precisely controlled delivery of possible therapeutic agents such as trophic factors and drugs. The potential of these chips for the study of neurological diseases is also discussed.

Animals↗

Slanted hole array beam profiler (SHArP)-a high-resolution portable beam profiler based on a linear aperture array.

We demonstrate a novel high-resolution portable beam profiler based on a slanted linear array of small apertures, termed a slanted hole array beam profiler (SHArP). The apertures are directly fabricated on a metal-coated CMOS imaging sensor. With a single linear scan, the aperture array can establish a virtual grid of sampling points for beam profiling. With our prototype, we demonstrate beam profiling of Gaussian beams over an area of 66.5 microm x 66.5 microm with a resolution of 0.8 microm (compare with the CMOS pixel size of 10 microm). The resolution can be improved into the range of submicrometers by fabricating smaller apertures. The good correspondence between the measured and calculated beam profiles proves the fidelity of our new beam profiling scheme.

Journal Article↗

Terahertz all-optical modulation in a silicon-polymer hybrid system.

Although gigahertz-scale free-carrier modulators have been demonstrated in silicon, intensity modulators operating at terahertz speeds have not been reported because of silicon's weak ultrafast nonlinearity. We have demonstrated intensity modulation of light with light in a silicon-polymer waveguide device, based on the all-optical Kerr effect-the ultrafast effect used in four-wave mixing. Direct measurements of time-domain intensity modulation are made at speeds of 10 GHz. We showed experimentally that the mechanism of this modulation is ultrafast through spectral measurements, and that intensity modulation at frequencies in excess of 1 THz can be obtained. By integrating optical polymers through evanescent coupling to silicon waveguides, we greatly increase the effective nonlinearity of the waveguide, allowing operation at continuous-wave power levels compatible with telecommunication systems. These devices are a first step in the development of large-scale integrated ultrafast optical logic in silicon, and are two orders of magnitude faster than previously reported silicon devices.

Journal Article↗

Microfluidic vias enable nested bioarrays and autoregulatory devices in Newtonian fluids.

We report on a fundamental technological advance for multilayer polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting channels located in different layers, are fabricated monolithically, in parallel, by simple and easy means. The resulting 3D connectivity greatly expands the potential complexity of microfluidic architecture. We apply the vias to printing nested bioarrays and building autoregulatory devices. A current source is demonstrated, while a diode and a rectifier are derived; all are building blocks for analog circuitry in Newtonian fluids. We also describe microfluidic septa and their applications. Vias lay the foundation for a new generation of microfluidic devices.

Dimethylpolysiloxanes↗

Electrically pumped two-dimensional Bragg grating lasers.

We demonstrate electrically pumped InGaAsP two-dimensional Bragg grating (2DBG) lasers with two line defects. The 2DBG structure uses a weak 2D index perturbation surface grating to control the optical modes in the plane of the wafer. Measurements of the 2DBG lasers show that modal control in both the longitudinal and transverse directions is due to the gratings and defects. The 2DBG lasers are promising candidates for single-mode, high power, and high efficiency large-area lasers.

Journal Article↗

Stray field magnetic resonance tomography using ferromagnetic spheres.

The methodology for obtaining two- and three-dimensional magnetic resonance images by using azimuthally symmetric dipolar magnetic fields from ferromagnetic spheres is described. We utilize the symmetric property of a geometric sphere in the presence of a large externally applied magnetic field to demonstrate that a complete two- or three-dimensional structured rendering of a sample can be obtained without the motion of the sample relative to the sphere. Sequential positioning of the integrated sample-sphere system in an external magnetic field at various angular orientations provides all the required imaging slices for successful computerized tomographic image reconstruction. The elimination of the requirement to scan the sample relative to the ferromagnetic tip in this imaging protocol is a potentially valuable simplification compared to previous scanning probe magnetic resonance imaging proposals.

Electromagnetic Fields↗

Nanofluidic tuning of photonic crystal circuits.

By integrating soft-lithography-based nanofluidics with silicon nanophotonics, we demonstrate dynamic, liquid-based addressing and high deltan/n (approximately 0.1) refractive index modulation of individual features within photonic structures at subwavelength length scales. We show ultracompact tunable spectral filtering through nanofluidic targeting of a single row of holes within a planar photonic crystal. We accomplished this with an optofluidic integration architecture comprising a nanophotonic layer, a nanofluidic delivery structure, and a microfluidic control engine. Variants of this technique could enable dynamic reconfiguration of photonic circuits, selective introduction of optical nonlinearities, or delivery of single molecules into resonant cavities for biodetection.

Journal Article↗

Patterning lines by capillary flows.

We report that capillary flows in an evaporating thin film create line patterns, with widths ranging from a few micrometers to less than 100 nm. Deliberate patterning of such lines requires contact-line pinning and the presence of foaming surfactants. Large-scale photolithography can guide and control these structures by creating pinning points and steering evaporation. We provide demonstrations of this process by making self-assembling lines of colloidal quantum dots and microspheres.

Animals↗

The analytical approach to polydimethylsiloxane microfluidic technology and its biological applications.

This review article discusses PDMS (polydimethylsiloxane) microfluidic devices and their biological applications. First, the already developed devices are classified from the viewpoints of underlying technology within a common logical framework comprising single-layer, multilayer, and integrated devices, as well as surface chemistry modifications of PDMS. Combinatorial techniques are applied to re-derive existing devices within this framework. Next, the relevant scales of both microfluidics and biology are compared, obtaining the promise and limitations of PDMS microfluidics. Finally, the body of work is reclassified in terms of addressed biological applications and compared to the standard methods in cellular and molecular biology, to offer insights for future devices and applications.

Animals↗

High-throughput multi-antigen microfluidic fluorescence immunoassays.

Here we describe the development of a high-throughput multi-antigen microfluidic fluorescence immunoassay system. A 100-chamber polydimethylsiloxane (PDMS) chip performs up to 5 tests for each of 10 samples. In this particular study system, the specificity of detection was demonstrated, and calibration curves were produced for C-reactive protein (CRP), prostate-specific antigen (PSA), ferritin, and vascular endothelial growth factor (VEGF). The measurements show sensitivity at and below clinically normal levels (with a signal-to-noise ratio >8 at as low as 10 pM antigen concentration). The chip uses 100 nL per sample for all tests. The developed system is an important step toward derivative immunoassay applications in scientific research and "point-of-care" testing in medicine.

Antigens↗

Magnetic nanostructures as amplifiers of transverse fields in magnetic resonance.

We introduce the concept of amplifying the transverse magnetic fields produced and/or detected with inductive coils in magnetic resonance settings by using the reversible transverse susceptibility properties of magnetic nanostructures. First, we describe the theoretical formalism of magnetic flux amplification through the coil in the presence of a large perpendicular DC magnetic field (typical of magnetic resonance systems) achieved through the singularity in the reversible transverse susceptibility in anisotropic single domain magnetic nanoparticles. We experimentally demonstrate the concept of transverse magnetic flux amplification in an inductive coil system using oriented nanoparticles with uni-axial magnetic anisotropy. We also propose a composite ferromagnetic/anti-ferromagnetic core/shell nanostructure system with uni-directional magnetic anisotropy that, in principle, provides maximal transverse magnetic flux amplification.

Journal Article↗

Hybrid superprism with low insertion losses and suppressed cross-talk.

We demonstrate with the two-dimensional finite-difference time-domain method that an adiabatic transition in a superprism with an interface along the [1 2 ] direction enhances the transmission through the superprism to more than 90% (-0.5 dB) over the wavelength range 1.47-1.68 mum , including the telecommunication C and L bands. We also show that diffraction governed by a quasinegative index of refraction inside the superprism can be used to obtain nearly transform-limited beam widths at the output of the superprism. The reduction of the beam width at the output suppresses cross-talk and greatly enhances the achievable frequency resolution of the superprism.

Journal Article↗

Composite nanowire-based probes for magnetic resonance force microscopy.

We present a nanowire-based methodology for the fabrication of ultrahigh sensitivity and resolution probes for atomic resolution magnetic resonance force microscopy (MRFM). The fabrication technique combines electrochemical deposition of multifunctional metals into nanoporous polycarbonate membranes and chemically selective electroless deposition of optical nanoreflector onto the nanowire. The completed composite nanowire structure contains all the required elements for an ultrahigh sensitivity and resolution MRFM sensor with (a) a magnetic nanowire segment providing atomic resolution magnetic field imaging gradients as well as large force gradients for high sensitivity, (b) a noble metal enhanced nanowire segment providing efficient scattering cross-section from a sub-wavelength source for optical readout of nanowire vibration, and (c) a nonmagnetic/nonplasmonic nanowire segment providing the cantilever structure for mechanical detection of magnetic resonance.

Journal Article↗

Nanomagnetic planar magnetic resonance microscopy "lens".

The achievement of three-dimensional atomic resolution magnetic resonance microscopy remains one of the main challenges in the visualization of biological molecules. The prospects for single spin microscopy have come tantalizingly close due to the recent developments in sensitive instrumentation. Despite the single spin detection capability in systems of spatially well-isolated spins, the challenge that remains is the creation of conditions in space where only a single spin is resonant and detected in the presence of other spins in its natural dense spin environment. We present a nanomagnetic planar design where a localized Angstrom-scale point in three-dimensional space is created above the nanostructure with a nonzero minimum of the magnetic field magnitude. The design thereby represents a magnetic resonance microscopy "lens" where potentially only a single spin located in the "focus" spot of the structure is resonant. Despite the presence of other spins in the Angstrom-scale vicinity of the resonant spin, the high gradient magnetic field of the "lens" renders those spins inactive in the detection process.

Magnetic Resonance Imaging↗

Surface-plasmon-enhanced light emitters based on InGaN quantum wells.

Since 1993, InGaN light-emitting diodes (LEDs) have been improved and commercialized, but these devices have not fulfilled their original promise as solid-state replacements for light bulbs as their light-emission efficiencies have been limited. Here we describe a method to enhance this efficiency through the energy transfer between quantum wells (QWs) and surface plasmons (SPs). SPs can increase the density of states and the spontaneous emission rate in the semiconductor, and lead to the enhancement of light emission by SP-QW coupling. Large enhancements of the internal quantum efficiencies (eta(int)) were measured when silver or aluminium layers were deposited 10 nm above an InGaN light-emitting layer, whereas no such enhancements were obtained from gold-coated samples. Our results indicate that the use of SPs would lead to a new class of very bright LEDs, and highly efficient solid-state light sources.

Crystallization↗

Coverage of anterior fossa in whole-brain irradiation.

PURPOSE: Whole-brain irradiation is indispensable in the treatment of several brain tumors and requires coverage of the entire subarachnoid space. Retrospective studies have revealed frequent recurrences in the frontobasal fossa above the cribriform plate (CP). We sought to determine how accurately the latter could actually be identified on lateral radiographs such as those used for radiotherapy planning. METHODS AND MATERIALS: The CP was localized by five radiation oncologists and five radiologists on lateral radiographs of 30 human skulls from an anatomic collection. Reference radiographs were acquired under identical conditions except for lead markers pointing to the CP and the ethmoid cells. The targeting accuracy was analyzed. RESULTS: In 39% (n = 116), the location of the CP was correctly estimated within 2 mm. Mislocations of 2-5, 5-10, and >10 mm were noted in 34% (n = 102), 20% (n = 61), and 7% (n = 21), respectively. Neither specialty nor experience (years of training) exerted a significant influence on targeting accuracy. If the roofs of the ethmoid cells formed prominent bony edges, they were mistaken for the CP in 37%. CONCLUSION: Lateral radiographs provide insufficient information to locate the CP accurately in whole brain irradiation. Additionally, localization was significantly impaired by prominent ethmoid cells.

Adult↗

Mode matching interface for efficient coupling of light into planar photonic crystals.

In order to integrate superdispersive elements based on photonic crystals, such as the superprism, with conventional integrated optics, insertion losses at the interface to the photonic crystal need to be reduced to an acceptable level. We describe a mode matching interface composed of cascaded diffraction gratings that generates the field profile of the photonic crystal Bloch mode from a slab mode. We calculate with three-dimensional finite-difference time-domain computation that by interposing such a multilayered grating between an unpatterned slab and a planar photonic crystal, the insertion efficiency is enhanced from 9% to 84%. Each diffraction grating consists of a row of holes and does not require any additional process steps from those used to fabricate the planar photonic crystal. In order to optimize the efficiency of the mode matching interface, constructive interference conditions are imposed between successive gratings and reflections from individual gratings are suppressed. We fabricate devices in silicon on insulator material and show experimental evidence of the Bloch mode structure and of the mode matching mechanism.

Journal Article↗